VCV000691710.8 - ClinVar

NM_001151.4(SLC25A4):c.742G>A (p.Asp248Asn)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (3)

3 out of 3 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001151.4(SLC25A4):c.742G>A (p.Asp248Asn)

Variation ID: 691710 Accession: VCV000691710.8

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4q35.1 4: 185146816 (GRCh38) [ NCBI UCSC ] 4: 186067970 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 12, 2019	Feb 15, 2026	Apr 11, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001151.4:c.742G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001142.2:p.Asp248Asn	missense
NC_000004.12:g.185146816G>A
NC_000004.11:g.186067970G>A
NG_013001.1:g.8554G>A
LRG_441:g.8554G>A
LRG_441t1:c.742G>A	LRG_441p1:p.Asp248Asn

... more HGVS ... less HGVS

Protein change

D248N

Other names

Canonical SPDI

NC_000004.12:185146815:G:A

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00002

Links

ClinGen: CA3156585 dbSNP: rs755597294 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SLC25A4		-	-	GRCh38 GRCh37	303	452

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Restrictive cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Aug 13, 2018	RCV000852560.1
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2	Uncertain significance (1)	criteria provided, single submitter	Oct 1, 2019	RCV001196354.2
not provided	Uncertain significance (1)	criteria provided, single submitter	Apr 11, 2025	RCV002538866.5

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Aug 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Restrictive cardiomyopathy	Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego Accession: SCV000995260.1 First in ClinVar: Oct 12, 2019 Last updated: Oct 12, 2019	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Uncertain significance (Oct 01, 2019) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2	Centre for Mendelian Genomics, University Medical Centre Ljubljana Accession: SCV001366955.2 First in ClinVar: Jul 04, 2020 Last updated: Jul 04, 2020	Comment: show This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: yes Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: yes

Uncertain significance (Apr 11, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002944890.4 First in ClinVar: Feb 07, 2023 Last updated: Feb 15, 2026	Comment: show This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 248 of the SLC25A4 protein (p.Asp248Asn). This variant is present in population databases (rs755597294, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SLC25A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 691710). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 248 of the SLC25A4 protein (p.Asp248Asn). This variant is present in population databases (rs755597294, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SLC25A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 691710). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs755597294 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026